Large-scale neural model for visual attention: integration of experimental single-cell and fMRI data

A computational neuroscience framework is proposed to better understand the role and the neuronal correlate of spatial attention modulation in visual perception. The model consists of several interconnected modules that can be related to the different areas of the dorsal and ventral paths of the visual cortex. Competitive neural interactions are implemented at both microscopic and interareal levels, according to the biased competition hypothesis. This hypothesis has been experimentally confirmed in studies in humans using functional magnetic resonance imaging (fMRI) techniques and also in single-cell recording studies in monkeys. Within this neuro-dynamical approach, numerical simulations are carried out that describe both the fMRI and the electrophysiological data. The proposed model draws together data of different spatial and temporal resolution, as are the above-mentioned imaging and single-cell results.     

Direct comparison of spontaneous functional connectivity and effective connectivity measured by intracortical microstimulation: an fMRI study in macaque monkeys

Correlated spontaneous activity in the resting brain is increasingly recognized as a useful index for inferring underlying functional-anatomic architecture. However, despite efforts for comparison with anatomical connectivity, neuronal origin of intrinsic functional connectivity (inFC) remains unclear. Conceptually, the source of inFC could be decomposed into causal components that reflect the efficacy of synaptic interactions and other components mediated by collective network dynamics (e.g., synchronization). To dissociate these components, it is useful to introduce another connectivity measure such as effective connectivity, which is a quantitative measure of causal interactions. Here, we present a direct comparison of inFC against emEC (effective connectivity probed with electrical microstimulation [EM]) in the somatosensory system of macaque monkeys. Simultaneous EM and functional magnetic resonance imaging revealed strong emEC in several brain regions in a manner consistent with the anatomy of somatosensory system. Direct comparison of inFC and emEC revealed colocalization and overall positive correlation within the stimulated hemisphere. Interestingly, we found characteristic differences between inFC and emEC in their interhemispheric patterns. Our results suggest that intrahemispheric inFC reflects the efficacy of causal interactions, whereas interhemispheric inFC may arise from interactions akin to network-level synchronization that is not captured by emEC.     

The effects of feature attention on prestimulus cortical activity in the human visual system

Covert attention affects prestimulus activity in the visual cortex. Although most studies investigating neural mechanisms of attention have focused on the effects of spatial attention, attention can also be directed to particular features. To investigate the spatiotemporal nature of feature attention, we measured subjects' brain activity using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) while subjects attended to color or motion of a stimulus based on a visual cue, which was presented 1 s before the stimulus onset. We used the hierarchical Bayesian method that allows us to estimate cortical currents with MEG and fMRI data in the order of millimeters and milliseconds. When subjects attended to color, activity within the color-sensitive area (fusiform gyrus) was selectively enhanced within the prestimulus period. By contrast, when subjects attended to motion, activity within the motion-sensitive area (middle temporal gyrus) was selectively enhanced during this period. This effect was not seen in frontal, parietal, and lower visual areas. Additionally, this effect was transient rather than sustained, suggesting that it differs from temporal aspects of spatial attention. These results suggest that, although both spatial and feature attention modulate prestimulus activity within specific visual areas, neural mechanisms underlying these effects might be different.     

Selective attention increases the dependency of cortical responses on visual motion coherence in man

Attention improves visual discrimination and consequently allows to discern stimuli with low signal-to-noise ratios that otherwise would remain undetected. We used magnetoencephalography (MEG) to test whether neuromagnetic responses recorded from occipito-temporal cortex, reflecting the size of visual motion signals embedded in noise (motion coherence), would mirror the perceptual changes induced by attention. Attention directed to a given hemifield increased and decreased the coherence modulation of the MEG response over contralateral and ipsilateral visual cortex, respectively, indicating a change in the neuronal signal-to-noise ratio at the population level.     

Determinants of work injuries in mines - an application of structural equation modelling

In spite of stringent regulations and much attention towards reducing risks in the physical environment, the mining industry continues to be associated with high levels of accidents, injuries and illnesses. Only engineering solutions to accident prevention are inappropriate unless coupled with focused attention to the attitudes and behaviours of the mineworkers in coping with the inherent physical, technical and situational risks. The present study identified these various risk factors and analysed their influences on work injury in a causal framework. Data were collected from an underground coalmine of India. The pattern and strength of relationships of 16 causal factors with work injuries were assessed through structural equation modelling. The case study results showed that negatively personified individuals are of major concern for safety improvement in the mine studied. They not only fail to avoid work injuries, they are unable to extend safe work behaviours in their work. The variable safety environment is negatively affected by personality, whereas social support has a positive relationship with safety environment. The variable job hazards appeared to have a significant relationship with job involvement, which has a negative relationship with work injury. Elimination of negative behaviours must be focused and committed by the mine safety management. Long term planning through (i) identification of negative individuals, (ii) proper councelling of adverse effects of negative behaviours, and (iii) special training with psychological treatment is highly required. Identification may begin while recruiting new workers through interview. Proper allocation of jobs (right person for right job) may be a judicial solution to this end.     

Modulation of LIP activity by predictive auditory and visual cues

The lateral intraparietal area (area LIP) contains a multimodal representation of extra-personal space. To further examine this representation, we trained rhesus monkeys on the predictive-cueing task. During this task, monkeys shifted their gaze to a visual target whose location was predicted by the location of an auditory or visual cue. We found that, when the sensory cue was at the same location as the visual target, the monkeys' mean saccadic latency was faster than when the sensory cue and the visual target were at different locations. This difference in mean saccadic latency was the same for both auditory cues and visual cues. Despite the fact that the monkeys used auditory and visual cues in a similar fashion, LIP neurons responded more to visual cues than to auditory cues. This modality-dependent activity was also seen during auditory and visual memory-guided saccades but to a significantly greater extent than during the predictive-cueing task. Additionally, we found that the firing rate of LIP neurons was inversely correlated with saccadic latency. This study indicates further that modality-dependent differences in LIP activity do not simply reflect differences in sensory processing but also reflect the cognitive and behavioral requirements of a task.     

Theoretical neuroanatomy: relating anatomical and functional connectivity in graphs and cortical connection matrices

Neuroanatomy places critical constraints on the functional connectivity of the cerebral cortex. To analyze these constraints we have examined the relationship between structural features of networks (expressed as graphs) and the patterns of functional connectivity to which they give rise when implemented as dynamical systems. We selected among structurally varying graphs using as selective criteria a number of global information-theoretical measures that characterize functional connectivity. We selected graphs separately for increases in measures of entropy (capturing statistical independence of graph elements), integration (capturing their statistical dependence) and complexity (capturing the interplay between their functional segregation and integration). We found that dynamics with high complexity were supported by graphs whose units were organized into densely linked groups that were sparsely and reciprocally interconnected. Connection matrices based on actual neuroanatomical data describing areas and pathways of the macaque visual cortex and the cat cortex showed structural characteristics that coincided best with those of such complex graphs, revealing the presence of distinct but interconnected anatomical groupings of areas. Moreover, when implemented as dynamical systems, these cortical connection matrices generated functional connectivity with high complexity, characterized by the presence of highly coherent functional clusters. We also found that selection of graphs as they responded to input or produced output led to increases in the complexity of their dynamics. We hypothesize that adaptation to rich sensory environments and motor demands requires complex dynamics and that these dynamics are supported by neuroanatomical motifs that are characteristic of the cerebral cortex.     

fMRI investigation of working memory for faces in autism: visual coding and underconnectivity with frontal areas

Brain activation and functional connectivity were investigated in high functioning autism using functional magnetic resonance imaging in an n-back working memory task involving photographic face stimuli. The autism group showed reliably lower activation compared with controls in the inferior left prefrontal area (involved in verbal processing and working memory maintenance) and the right posterior temporal area (associated with theory of mind processing). The participants with autism also showed activation in a somewhat different location in the fusiform area than the control participants. These results suggest that the neural circuitry of the brain for face processing in autism may be analyzing the features of the face more as objects and less in terms of their human significance. The functional connectivity results revealed that the abnormal fusiform activation was embedded in a larger context of smaller and less synchronized networks, particularly indicating lower functional connectivity with frontal areas. In contrast to the underconnectivity with frontal areas, the autism group showed no underconnectivity among posterior cortical regions. These results extend previous findings of abnormal face perception in autism by demonstrating that the abnormalities are embedded in an abnormal cortical network that manages to perform the working memory task proficiently, using a visually oriented, asocial processing style that minimizes reliance on prefrontal areas.     

Modulation of NMDA receptor function by ketamine and magnesium. Part II: interactions with volatile anesthetics

Mg2+ and ketamine interact superadditively at N- methyl-D-aspartate (NMDA) receptors, which may explain the clinical efficacy of the combination. Because patients are usually exposed concomitantly to volatile anesthetics, we tested the hypothesis that volatile anesthetics interact with ketamine and/or Mg2+ at recombinantly expressed NMDA receptors. NR1/NR2A or NR1/NR2B receptors were expressed in Xenopus oocytes. We determined the effects of isoflurane, sevoflurane, and desflurane on NMDA receptor signaling, alone and in combination with S(+)-ketamine (4.1 microM on NR1/NR2A, 3.0 microM on NR2/NR2B) and/or Mg2+ (416 microM on NR1/NR2A, 629 microM on NR1/NR2B). Volatile anesthetics inhibited NR1/NR2A and NR1/NR2B glutamate receptor function in a reversible, concentration-dependent, voltage-insensitive and noncompetitive manner (half-maximal inhibitory concentration at NR1/NR2A receptors: 1.30 +/- 0.02 minimum alveolar anesthetic concentration [MAC] for isoflurane, 1.18 +/- 0.03 MAC for desflurane, 1.24 +/- 0.06 MAC for sevoflurane; at NR1/NR2B receptors: 1.33 +/- 0.12 MAC for isoflurane, 1.22 +/- 0.08 MAC for desflurane, and 1.28 +/- 0.08 MAC for sevoflurane). On both NR1/NR2A and NR1/NR2B receptors, 50% inhibitory concentration for volatile anesthetics was reduced approximately 20% by Mg2+, approximately 30% by S(+)-ketamine, and approximately 50% by the compounds in combination. Volatile anesthetic effects on NMDA receptors can be potentiated significantly by Mg2+, S(+)-ketamine, or-most profoundly-both. Therefore, the analgesic effects of ketamine and Mg2+, are likely to be enhanced in the presence of volatile anesthetics. IMPLICATIONS: Clinically relevant concentrations of volatile anesthetics inhibit functioning of N-methyl-D-aspartate receptors expressed recombinantly in Xenopus oocytes. This inhibition is reversible, concentration-dependent and voltage-insensitive, and results from noncompetitive antagonism of glutamate/glycine signaling. In addition, these effects can be potentiated significantly by co-application of either Mg2+, S(+)-ketamine, or--most profoundly--both.     

Tuning curve shift by attention modulation in cortical neurons: a computational study of its mechanisms

Physiological studies of visual attention have demonstrated that focusing attention near a visual cortical neuron's receptive field (RF) results in enhanced evoked activity and RF shift. In this work, we explored the mechanisms of attention induced RF shifts in cortical network models that receive an attentional 'spotlight'. Our main results are threefold. First, whereas a 'spotlight' input always produces toward-attention shift of the population activity profile, we found that toward-attention shifts in RFs of single cells requires multiplicative gain modulation. Secondly, in a feedforward two-layer model, focal attentional gain modulation in first-layer neurons induces RF shift in second-layer neurons downstream. In contrast to experimental observations, the feedforward model typically fails to produce RF shifts in second-layer neurons when attention is directed beyond RF boundaries. We then show that an additive spotlight input combined with a recurrent network mechanism can produce the observed RF shift. Inhibitory effects in a surround of the attentional focus accentuate this RF shift and induce RF shrinking. Thirdly, we considered interrelationship between visual selective attention and adaptation. Our analysis predicts that the RF size is enlarged (respectively reduced) by attentional signal directed near a cell's RF center in a recurrent network (resp. in a feedforward network); the opposite is true for visual adaptation. Therefore, a refined estimation of the RF size during attention and after adaptation would provide a probe to differentiate recurrent versus feedforward mechanisms for RF shifts.     

Validity of primary motor area localization with fMRI versus electric cortical stimulation: A comparative study

Background  

Functional magnetic resonance imaging (fMRI) is a widely used method for research and visualization of the brain function. However, its clinical use is still limited. Our objective was to study fMRI reliability in localizing the primary hand motor cortex (M1) under pathological conditions caused by the proximity of a brain tumour. The results were then compared with standard technique of cortical function mapping—electric cortical stimulation (ECS).     

Effects of glucocorticoids on skeletal growth in rabbits evaluated by dual-photon absorptiometry,microscopic connectivity and vertebral compressive strength

The effects of corticosteroid on bone were examined in female growing rabbits treated with 0.7 mg/kg per day prednisolone for 5 months. The evolution of whole-body total bone mineral measured by dual-photon absorptiometry showed a significant difference between the prednisolone-treated group and the control group from the first to the fifth month. The histomorphometric profile of corticosteroid-induced osteoporosis was observed, in particular the lower bone volume and thinner and fewer trabecular plates. Mechanical tests are possible on rabbit vertebrae and showed a very significant difference in bone strength between the prednisolone-treated and control groups, and a good correlation between mechanical tests and histomorphometric or densitometric results. This bone corticosteroid model shows that vertebral compression tests are possible on rabbit lumbar vertebrae. It may contribute to a better evaluation of corticosteroid treatments.     

Separating intra-modal and across-modal training effects in visual working memory: an fMRI investigation

Working memory training is a useful tool to examine dissociations between specific working memory processes. Although current models propose a distinction between modality-specific working memory processes, to our knowledge no study has directly examined the effects of visual versus auditory working memory training. Functional magnetic resonance imaging was used to investigate whether visual working memory processes can be trained specifically and whether those effects can be separated from across-modal training effects. We found decidedly larger training gains after visual working memory training compared with auditory or no training on a visual 2-back task. These effects were accompanied by specific training-related decreases in the right middle frontal gyrus arising from visual training only. Likewise, visual and auditory training led to decreased activations in the superior portion of the right middle frontal gyrus and the right posterior parietal lobule. We infer that the combination of effects resulted from increased neural efficiency of intra-modal (visual) processes on the one hand and of across-modal (general control) processes on the other hand. Therefore, visual processes of working memory can be trained specifically, and these effects can be functionally dissociated from alterations in general control processes common to both working memory trainings.     

Function and connectivity in human primary auditory cortex: a combined fMRI and DTI study at 3 Tesla

Human primary auditory cortex (PAC) is functionally organized in a tonotopic manner. Past studies have used neuroimaging to characterize tonotopic organization in PAC and found similar organization as that described in mammals. In contrast to what is known about PAC in primates and nonprimates, in humans, the structural connectivity within PAC has not been defined. In this study, stroboscopic event-related functional magnetic resonance imaging (fMRI) was utilized to reveal mirror symmetric tonotopic organization consisting of a high-low-high frequency gradient in PAC. Furthermore, diffusion tensor tractography and probabilistic mapping was used to study projection patterns within tonotopic areas. Based on earlier physiological and histological work in nonhuman PAC, we hypothesized the existence of cross-field isofrequency (homotopic) and within-field non-isofrequency (heterotopic)-specific axonal projections in human PAC. The presence of both projections types was found in all subjects. Specifically, the number of diffusion tensor imaging (DTI) reconstructed fibers projecting between high- and low-frequency regions was greater than those fibers projecting between 2 high-frequency areas, the latter of which are located in distinct auditory fields. The fMRI and DTI results indicate that functional and structural properties within early stages of the auditory processing stream are preserved across multiple mammalian species at distinct evolutionary levels.     

Antinociceptive actions of intrathecal xylazine: interactions with spinal cord opioid pathways

We have studied rats with chronically implanted subarachnoid catheters. Xylazine, an alpha 2 adrenoceptor agonist, was injected intrathecally and nociceptive thresholds measured at two skin sites: the tail and the neck. Intrathecal xylazine (dose range 24.3-389 nmol) produced increases in electrical thresholds for nociception in the tail without any change in the neck; this observation suggested that the antinociceptive action of this drug was confined to the caudal part of the spinal cord responsible for tail innervation. The magnitude of this effect was dose-dependent. Tail flick latency also increased in these rats and the antinociceptive effects were antagonized in a dose- dependent manner by the selective alpha 2 adrenoceptor antagonist idazoxan (dose range 6.7-540 nmol). Intrathecal idazoxan also suppressed the increase in tail flick latency caused by the mu opioid agonist fentanyl (0.74 nmol) given intrathecally. This effect was also dose-dependent. The idazoxan dose-response curve for this suppression of fentanyl antinociception assessed with tail flick latency was the same as that for suppression of xylazine. In contrast, the antinociceptive effects of intrathecal xylazine were not affected by concurrent administration of opioid or GABAA antagonists. We conclude that intrathecal xylazine produced spinally mediated antinociceptive effects by combination with spinal cord alpha 2 adrenoceptors and that neither opioid nor GABA-containing propriospinal neurones were involved in the mediation of this effect. However, alpha 2 adrenoceptors in the spinal cord appear to be involved with antinociception produced by intrathecal fentanyl.      

Corticocortical associative neurons expressing latexin: specific cortical connectivity formed in vivo and in vitro.

Latexin, a carboxypeptidase A inhibitor, is expressed in a subset of neurons in the infragranular layers of the lateral cortex in the rat. We here show that latexin-expressing neurons exhibit ultrastructural features common to cortical pyramidal neurons. We show in combined retrograde tracing and immunofluorescent experiments that latexin-expressing neurons contribute to specific corticocortical pathways. Thus, injections of the retrograde tracer fluorogold into either the primary somatosensory (SI) or the primary motor (MI) cortical area labeled many latexin-expressing neurons in the infragranular layers of the secondary somatosensory (SII) and visceral sensory (Vi) areas. In contrast, tracer injections involving the thalamus, striatum, or contralateral SII and Vi exclusively labeled latexin-nonexpressing neurons in both the SII and Vi. Finally, we show that the correct corticocortical projections can be formed in organotypic slice cultures in vitro from latexin-expressing neurons: when slices of developing SII were cocultured with those from the SI and the thalamus, latexin-immunoreactive neurons in the SII projected preferentially to their normal SI target. The specific connectivity formed in vivo and in vitro by this molecularly distinct neuronal population reveals its characteristic manner of cortical organization and provides a unique model system to analyze mechanisms underlying the formation of precise corticocortical pathways.     

Human cortical distal nephron: distribution of electrolyte and water transport pathways

The exact distributions of the different salt transport systems along the human cortical distal nephron are unknown. Immunohistochemistry was performed on serial cryostat sections of healthy parts of tumor nephrectomized human kidneys to study the distributions in the distal convolution of the thiazide-sensitive Na-Cl cotransporter (NCC), the beta subunit of the amiloride-sensitive epithelial Na channel (ENaC), the vasopressin-sensitive water channel aquaporin 2 (AQP2), and aquaporin 3 (AQP3), the H(+) ATPase, the Na-Ca exchanger (NCX), plasma membrane calcium-ATPase, and calbindin-D28k (CaBP). The entire human distal convolution and the cortical collecting duct (CCD) display calbindin-D28k, although in variable amounts. Approximately 30% of the distal convolution profiles reveal NCC, characterizing the distal convoluted tubule. NCC overlaps with ENaC in a short portion at the end of the distal convoluted tubule. ENaC is displayed all along the connecting tubule (70% of the distal convolution) and the CCD. The major part of the connecting tubule and the CCD coexpress aquaporin 2 with ENaC. Intercalated cells, undetected in the first 20% of the distal convolution, were interspersed among the segment-specific cells of the remainder of the distal convolution, and of the CCD. The basolateral calcium extruding proteins, Na-Ca exchanger (NCX), and the plasma membrane Ca(2+)-ATPase were found all along the distal convolution, and, in contrast to other species, along the CCD, although in varying amounts. The knowledge regarding the precise distribution patterns of transport proteins in the human distal nephron and the knowledge regarding the differences from that in laboratory animals may be helpful for diagnostic purposes and may also help refine the therapeutic management of electrolyte disorders.     

A neural model of motion processing and visual navigation by cortical area MST

Cells in the dorsal medial superior temporal cortex (MSTd) process optic flow generated by self-motion during visually guided navigation. A neural model shows how interactions between well-known neural mechanisms (log polar cortical magnification, Gaussian motion-sensitive receptive fields, spatial pooling of motion-sensitive signals and subtractive extraretinal eye movement signals) lead to emergent properties that quantitatively simulate neurophysiological data about MSTd cell properties and psychophysical data about human navigation. Model cells match MSTd neuron responses to optic flow stimuli placed in different parts of the visual field, including position invariance, tuning curves, preferred spiral directions, direction reversals, average response curves and preferred locations for stimulus motion centers. The model shows how the preferred motion direction of the most active MSTd cells can explain human judgments of self-motion direction (heading), without using complex heading templates. The model explains when extraretinal eye movement signals are needed for accurate heading perception, and when retinal input is sufficient, and how heading judgments depend on scene layouts and rotation rates.     

Changes in fMRI activation following rehabilitation of reading and visual processing deficits in subjects with traumatic brain injury

In this case series fMRI was used to examine activation patterns during presentation of a reading comprehension (RC) task in three adult subjects with a history of severe traumatic brain injury (TBI). These subjects received cognitive rehabilitation therapy (CRT) for visual processing and acquired reading deficits. fMRI and neuropsychological testing occurred pre- and post-rehabilitation. The study's objective was to evaluate the neurobiological changes using fMRI occurring with CRT and to compare these results to repeat fMRI in matched control subjects. While improvements in neuropsychological testing occurred post-CRT, diffuse and variable activation patterns in the subjects with TBI were still demonstrated when compared to the control subjects repeat imaging. Multiple networks exist to accomplish the complex task of sentence reading and rehabilitation of the cognitive components of reading, such as visual processing; in subjects with TBI, can alter the activation pattern demonstrated during reading comprehension in subjects many years post-injury. This is the first demonstration of changes in network activation patterns post-CRT in patients with severe, chronic TBI on an fMRI task shown to have imaging stability in a normal control sample.